Therapeutic composition



Patented May 5, 1942 S PATENT Samuel 8. Johnson, Uniouto, Pen, assignci'to Iii. Neel Gordon, New York, N. Y.

No Drawing.

l (Claims.

This invention relates to medicinal preparaticns particularly efiectivein the treatment of burns, eczemo, impetigo end diseases or the skin.

I have discovered that the ortho, pure. and mete nitro phenols, whenapplied to the skin, not only have strong therapeutic properties such asrenders them valuable as antiseptic and germicidol scents but also arecharacterized by the feet thot they are non-toxic, non-irritant endnon-destructive of tissue. in addition, I have Application February 21,1939, Serial No. 25?,661

found that the ortho and to less extent the meta.

' nitro phenols hove the ability to ropidly penetrate the slain end beabsorbed by the blood of the human body. This capacity oi the ortho andmeta nitro phenols to rapidly peneti'ete the skin results in increasedgermicidal activity thereof at the some time that it insures the promptend complete elimination oi these substances from the body by way of thekidneys. Also, the use of the ortho or metal nitro phenol in combinationwith porn nitro phenol imports to the combination penetrating propertieswhich the pore nitro phenol does not possess of itself, no the result ofwhich the pain nitro phenol,

which has strong antiseptic and germicidal properties, is carrieddirectly into the body tissues where it serves most effectively tosupplement the analgesic action of the ortho or mete nitro phenol.

Tests conducted over on extensive perio have conclusively demonstratedthat compoul. pared in accordance with the present hive end whichprimarily include as the therapeutic egcnt either ortho, porn or metenitro phenol or combination thereof are highly efiective when locallyapplied in the treatment of skin burns one cuts as well as in thetreatment of eczema, impetigo and other slain irritations, in all ofwhich cases the active ingredient nets to reduce infection, relieve painand soreness, retard blistering and restore the skin to healthycondition with the formation of a minimum of scar tissue even in thecase of severe burns and it is accordingly among the objects of thepresent invention to provide a medicinol preparation containing one ormore of the isomeric mono nitro phenols (i. e. ortho, para. end/or metanitro phenol) as the active ingredient for the treatment of skinlimitations and wounds as aforesaid, which prep oration may be in theform of a. semi-solid ointmerit, such as a salve, or in the form of a.liquid ointment, or in the form of e. tincture for application locallyto the affected area to be treated.

-Where the medicinal preparation or the present invention is in the tomof a salve, the bulk of the preparation may consist of oily suiteoleointment base such as petrolotum, petroleum jelly or any other suitableunguent, such es n cold or vanishing cream, to provide at resuitontcomposition which is of semi-solid cons tenet. Where, on the other hand,the preparation is de= sired to be in the form at s. liuuid the hosethereof may consist principally medicinal oil, such as White mineral or.or olive oil. Where the preparation is in the form of s tincture, thebase thereof may consist oi oi coho! or a solution. thereof. In anycase, only relatively small quantity of the active ingredient, i. e.,ortho, pore end/or mete nitro phone" I quired to be mixed with theointment h preferable proportion being one port ectlve ingredient tothirty-three ports of the ointmetal; base. It is to be understood, oi cothis proportion may be "varied Within rec oust Wide limits because apreparation contouring much as fifty percent by weight of the cot.ingredient may be employed without any he. lui results, while e.preparation contei little as one-tenth off one percent of ingredient maystill produce very tenet sults. v

The isomeric mono nitro phenols me well known substances, although thepore niti'o phenols are more readily avail. com mercislly than is theroots. nitro phenol. While the preparation or production of these soforms no part oi present inventiol hich. relates to the employmentthereof in the 2-, rotion oi a new medicinal compound, it is thoughtadvisable to describe herein preferred methods which may "be employed inobtaining the isomeric mono nitro phenols for use in nccordonce with thepresent invention.

Thus, in the production of the ortho end porn nitzo phenols, eightygrams or" sodium nitrate is initially dissolved in two hundred creme, ofheated water. Upon cooling of this initial sodium nitrate solution, onehundred grams of concentrated sulphuric acid is added thereto and thesolution is stirred until it is cooled to o tern perature ofapproximately 25 degrees C. Thereafter, and while this solution ofsodium nitrate and sulphuric acid is maintained at e tempera,- ture ofbetween 25 degrees C. and 30 degrees 6., there is added to the solutiondrop by drop 2.-

mixture of phenol melted in alcohol, this latter mixture being in theproportion of fifty groms of crystallized phenol melted in five grams oialcohol in the'presence of heat.

The resultant mixture (of the phenol in the hlond V sodiumnitrate-sulphuric acid solution) is then is preferable to employapproximately 80 percent oi the ortho nitro phenol to 20% of the paranitro phenol, although the ratio of ortho to para .nitro phenol may beas low as one to one with good results. However, it is not deemeddesirable to employ less ortho nitro phenol than para nitro phenol,because in such case there is a tendency The ortho nitro phenoldistillate is cooled and.

filtered, following which the ortho nitro phenol residue is washed withwater, pressed out on a porous plate and dried in a desiccator.

The non-volatile para nitro phenol, which remained in the vessel fromwhich the ortho nitro phenol was removed by distillation as aforesaid,

is then recovered as follows. After cooling the para nitro phenolmixture remaining in the vessel, the undissolved substances ofthemixture are filtered and the filtrate thus obtained is boiled for 15minutes with grams of animal charcoal, the water as it evaporates duringthis boiling process being replaced withfresh water. The charcoal isthen filtered oil and the filtrate allowed to stand over night whereuponthe para nitro phenol separates out or the solution in the form of longcolorless needles.

The production of the isomer meta nitro phenol is efiected by reducingmeta di-nitrobenzene to meta nitro analine and then treating thesolution of the latter in an excess of dilute sulphuric acid andthereafter with nitrous acid, preferably by bubbling the latter ingaseous form through the sulphuric acid solution of the meta nitroanaline. The solution of the diazonium. salt thus obtained is thenslowly heated to boiling resulting in the production of meta nitrophenol which is purified by recrystallization from water.

It will be understood, of course, .that the isomeric mono nitro phenolsmay be produced by methods other than those herein described, thepresent invention being concerned with the utilization of these phenolsin the compounding of medicinal preparations having high therapeuticproperties and wherein the para nitro phenol coacts with and supplementsthe ortho nitro phenol when combined therewith to provide results notobtainable when either the para nitro phenol or the ortho nitro phenolis employed alone. Thus, I have found that while the para nitro phenolhas marked antiseptic and germicidal properties, it does not have anypenetrating characteristics per se. On the other hand, I have found thatthe ortho nitro phenol not only has decidedly analgesic properties butalso is possessed of ahigh tissue-penetrating power. I have furtherfound that when the para and ortho nitro phenols are combined, thelatter serves as a carrier or vehicle for the former and thus eflfects apenetration of the para nitro phenol through the skin and into the bodytissue. This is believed to be due to the fact that the amnity betweenthe-ortho and para nitro phenols is somuch greater than that existingbetween para nitro phenol and the body tissues, in consequence of whichthe para nitro phenol is readily conveyed into the body tissue togetherwith the ortho nitro phenol.

'Acccrdingly, where the medicinal preparation is desired to haveantiseptic, analgesic and tissuepenetrating properties, the para andortho nitro phenols are mixed together and employed in combination asthe active therapeutic agent of the medicinal preparation. When socombined, it

for the latter to crystallize out of solution. Whenthe ortho nitrophenol and para nitro phenol are combined to constitute jointly theactive ingredient of the medicinal preparation, it is essential thattheir proportions be such that the ortho nitro phenol is suflicient toeffect the desired penetration of the combined active ingredient intothe body tissues and at the same time facilitate complete dissolution ofthe para nitro phenol in the supporting vehicle or solvent (e. g.petrolatum, mineral oil, alcohol) for the active ingredient.

As one example of a medicinal preparation compounded in accordance withthe present invention, the following formula may proportions statedbeing by weight:

Parts Olive oil 33 Para nitro phenol 0.2 Ortho nitro phenol 0.8

total.

ingredient of the medicinal compound any one of the isomer mono nitrophenols. However, in

such case when the para nitrophenol is utilized alone, the preparationis lacking in tissue pen'e- I trating powers and is to be consideredeffective only as an antiseptic and germicide; 0n the other hand, whenthe ortho nitro phenol is utilized alone, the preparation containing itas the active ingredient is possessed of marked tissue-penetratingproperties and serves effectively as an analgesic only.

As regards the meta nitro phenol, due to the fact that it is diiilcultand expensive to produce and, therefore, is not readily availableoommercially, its 'use as the active ingredient in medicinalpreparations compounded in accordance with the present invention is nrestricted. However, in the absence of cost considerations, the metanitro phenol may well be employed as the active medicament either aloneor in combination with the para nitro phenol. While meta nitro phenolis-not as soluble as ortho nitro phenol and, therefde, involves somegreater difliculty in incorporating it in the hintment or tincture base,it in itself w w the combined antiseptic, analgesic andtissue-penetrating properties of the para and ortho nitro phenols,although to lesser extent, and accordingly where the meta nitro phenolis employed alone the preparation containing it is quite effective as atissue-penetrating antiseptic and analgesic. a

It is to be understood that the proportions of the ingredients of thepreparation of the present invention, as well as the nature thereof, maybe varied within rather wide limits as indicated 7 hereinbefore withoutdeparting from the general principles or real spirit of the invention,and that while the isomer mono nitro phenols hereinbefore referred toconstitute the principal.

active ingredients of thepreparation, other inbe given, the

1 part gredients not affecting th stability or emcacy of the preparationmay be used in addition thereto.

What is claimed as new and useful is:

1. A therapeutic composition comprising the ortho and para. isomers ofmono nitro phenol dissolved in combination in a, vehicle capable ofbeing applied locally to afiected parts of the skin, said vehicleconstituting approximately 33 parts and the combined ortho and. paranitro phenols constituting approximately 1 part oi the composition, andthe ortho nitro phenol and the para nitro phenol being present in thecomposition in the ratio of approximately i parts of the former to 1part of the latter.

2. A therapeutic composition comprising the ortho and para isomers ofmono nitro phenol dissolved in combination in a vehicle capable of beingapplied locally to affected parts of the skin, the combined ortho andpars nitro phenols constituting the smaller part of the composition byweight and beingpresent in said composition in the ratio ofapproximately 4 parts of the ortho nitro phenol to 1 part of the vparanitro phenol.

3. A therapeutic composition according to claim 2 wherein said vehicleis in the form of an oleaginous base.

4. A therapeutic composition according to claim 2 wherein said vehicleis in the form oie tincture-forming solvent.

SAMUEL c. JQHNSON.

